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The present study examined the cytotoxicity and magnetic resonance imaging (MRI) distribution of cancer-targeted, MRI-visible polymeric micelles that encapsulate doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) and are conjugated with glucose as a targeting ligand. In this study, the micelles were investigated the clinical potential of glucose-micelles, in vitro cytotoxicity assays of nonencapsulating or SPIO-and-DOX-coencapsulating micelles were performed on L929 mouse fibroblasts, and we found that glucose-micelles did not exert in vitro cytotoxic effects. Next, in vitro MRI detectability of glucose SPIO micelles was evaluated at the loaded SPIO content of 2.5% and 50%, and it was found that glucose-micelles can increase MRI relaxivity (r 2 *) at high SPIO loading. Furthermore, 50% SPIO micelles persisted in the blood circulation for up to 5 days (slow liver clearance) as determined by in vivo MRI. For in vivo toxicity evaluation, 50% SPIO/DOX micelles at a dose up to 18 (mg DOX)/(kg body weight) showed no impact on animal health according to clinical chemistry and clinical hematology laboratory testing. Altogether, these results indicate that glucose-micelles can serve as an effective and safe drug delivery system.

Background: Semi-synthetic andrographolide analogue (19-triphenylmethyl ether andrographolide, AG 050) is a C-19 substituted andrographolide which is the major constituent from Andrographis Paniculata Nees (Acanthaceae). The analogue has previously been reported to be highly cytotoxic against several cancer cell lines. Nevertheless, its poor water solubility limits clinical applications of this compound., Objectives: To improve the aqueous solubility and bioavailability of AG 050 by protonation and encapsulation in poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-b-PLA) polymeric micelles., Materials and Methods: PEG-b-PLA micelle was employed as a nanocarrier for AG 050. The physicochemical properties and in vitro cytotoxicity against cholangiocarcinoma (CCA) (KKU-M213) cell line were done in this study., Result and Discussion: Hydrochloride salt of AG 050 (AG 050-P) greatly enhanced the solubility of this compound (15-fold). PEG-b-PLA was able to encapsulate AG 050-P in hydrophobic core with a significant increase in the amount of AG 050-P in aqueous solution (280-fold). Film sonication method provided greater results in drug-loading study as compared to micelles via solvent evaporation. In addition, the encapsulated AG 050-P exhibited sustained release pattern and excellent cytotoxicity activity against KKU-M213 with IC50 of 3.33 µM., Conclusion: Nanoencapsulation of AG 050-P implicated its potential development for clinical use in CCA treatment.